Download Neova® Creme de la Copper Combats Photodamage with DNA

Creme de la Copper
Neova® Creme de la Copper Combats Photodamage with
DNA Repair and Copper Peptide Technologies
Leonard M. Patt, Ph.D., Procyte, A PhotoMedex Company
147 Keystone Drive, Montgomeryville, PA 18936
Abstract
Neova® Creme de la Copper now combines an advanced form of DNA repair (Mitosomes) in combination with
Copper Peptide Complex® to fight the signs of aging and help restore skin’s youthful texture. This new formulation
continues to provide the protection and regeneration properties of the advanced ceramides of Skinmimics®.
Introduction
Copper Peptide Complex®
Wrinkles, puffiness, and dark circles under the
eyes are not very desirable features for most
people despite the fact that they are thought to
be inevitable results of aging and environmental
stress and damage. Wrinkles, of course, are
caused in part by the natural slowdown of repair
of the underlying extracellular matrix (ECM)
of the skin. The resulting accumulation of fine
lines, wrinkles, and sagging skin, can add to an
increased appearance of age.
Copper is essential to vital cellular and enzyme
processes required for human health, and is the
third most abundant trace metal in the body,
after iron and zinc. Since the 1830s, copper has
been known to be an essential nutrient. It was
found that copper plays a key role in several of
the body’s essential enzyme systems needed
for tissue repair and other biological responses.
These copper-based enzyme systems allow tissue
to repair itself, blood vessels to form, wounds to
close and inflammation to decrease. Copper is
now known to be critical to the normal repair and
healing process in all tissue, including connective
tissues that comprise human skin, internal organs
and bones.
DNA damage is a critical aftermath of UV irradiation
due to sunlight exposure and contributes to many
of the visible aspects of photoaging. Exposure to
UVB causes the formation of thiamine dimmers.
DNA damage can also come about during the
normal process of cellular metabolism and
respiration.
DNA repair refers to a collection of processes used
by a cell to identify and correct damage to the
DNA from either normal cellular processes or UV
radiation. The DNA repair process is constantly
active as the cells respond to damage in the DNA
structure. The rate of DNA repair is dependent
on many factors such as the type of cell, the age
of the cell, and the cellular environment. If a cell
accumulates a large amount of DNA damage
with insufficient repair, it may become dormant
(senescence), initiate programmed cell death
(apoptosis), or start unregulated cell proliferation
(cancer).
Creme de la Copper now combines an advanced
form of DNA repair (Mitosomes) along with
Copper Peptide Complex technology to fight the
signs of aging and help restore skin’s youthful
texture.
The formulation also includes the
protection and regeneration properties of the
advanced ceramides present in Skinmimics.
The Copper Peptide Complex in Creme de la
Copper is a tripeptide (glycyl-L-histidyl-L-lysine)
complexed with copper. The tripeptide was
originally isolated from the albumin fraction
of human serum1. It was subsequently shown
that the peptide existed as the copper complex
and enhanced the uptake of copper by cells2-4.
The glycyl-L-histidyl-L-lysine peptide sequence
is found in several proteins associated with
the extracellular matrix including the large
extracellular matrix protein termed SPARC and
may liberated by endogenous proteolysis or
cleavage of these proteins during the repair and
regeneration processes5-8. These small peptides
liberated from the extracellular matrix were
termed matrikines.
Skin health, dermal wound healing and general
soft tissue repair requires many of the same
biological processes such as reconstitution of an
extracellular matrix and increased blood from
(angiogenesis). Copper is utilized by essentially
every cell and organ; resulting in the formation of
© 2010 PhotoMedex. All Rights Reserved.
1
Creme de la Copper
As shown below, the activities of copper and
copper peptide are all essential to maintaining
skin health and reversing the signs of aging.
Activities of Copper and Copper Peptide
Scientific Studies
Collagen
Glycosaminoglycans
Elastin
Angiogenesis
Growth Factors
Matrix Metalloproteases
Enhance
Enhance
Enhance
Enhance
Enhance
Enhance
Performance Evaluations
Collagen
Skin Laxity
Skin Clarity
Skin Appearance
Fine Lines & Wrinkles
Skin Density
Skin Thickness
Enhance
Improve
Improve
Improve
Reduce
Appearance
Increase
Increase
Mitosomes
Mitosomes contain a DNA repair enzyme that
recognizes the most common form of oxidative
damage to DNA and initiates the repair process.
Mitosomes contain an enzyme (OGG1 for
8-oxoguanine DNA glycosylase 1) produced from
the common plant Arabidposis that recognizes
this damaged base (8-oxo-guanine) and initiates
its removal22-23.
2
80%
60%
40%
20%
Mitosomes 6 hr
Mitosomes 2 hr
Vehicle 6 hr
Vehicle 2 hr
None 6 hr
0%
None 2 hr
More importantly, Copper Peptide Complex,
formulated in a wide variety of cosmetic
preparations, has shown to both stimulate
collagen production and to reduce the visible
signs of aging, improve skin laxity, clarity, and
appearance, reduce the appearance of fine lines
and wrinkles, and to increase skin density and
thickness both on the face and eye area18-21.
100%
None 0 hr
In numerous studies, copper peptides have been
shown to promote new blood vessel growth,
enhance the expression of growth factors,
activate matrix metalloproteases, and stimulate
the formation of new collagen, elastin, and
glycosaminoglycan components of tissue to
accelerate the repair process11-17.
These radicals damage DNA by oxidizing its
nucleotide bases from to form 8-oxo-guanine.
Mitosomes shorten the time for nucleus DNA
repair from 24 hours to 2 hours, Figure 1
Mitosomes tested at 0.3% repair 75% of the
oxidative damage on DNA. In vitro testing at
0.5% shows that Mitosomes repair DNA in the
mitochondria, Figure 1.
Percentage DNA Damage
important copper-dependent enzymes - including
cytochrome C oxidase (energy production),
superoxide dismutase (antioxidation) and lysyl
oxidase (cross-linking of elastin and collagen in
skin)9-10.
Figure 1. Mitosomes Increase DNA Repair
In vitro testing has shown that 1% Mitosomes
completely repaired 8-oxo-guanine in cells in 2
hours, while 0.3% completed repair in about 3
hours22.
Mitochondrial DNA protection is also important to
anti-aging activity. Damage from oxygen radicals
is a main factor in aging. These reactive oxygen
species come from pollutants in the environment,
from UV-A induced reactions in skin, and from the
body’s own stress responses. In addition, oxygen
radicals are the inevitable side-effect of energy
mitochondria. The accumulation of damage to
mitochondria is considered an important element
of aging.
A vital feature of the Mitosomes enzyme is that
it also protects mitochondria. The enzyme has a
“mitochondrial localization signal” (MLS), which
is recognized by the cells transport system, and
guides it into mitochondria. This ability allows
Mitosomes to repair the DNA in mitochondria
after oxidative damage which occurs during
normal cellular respiration.
Skinmimics®
Skinmimics was designed to provide a
combination of protection, prevention, and
regeneration cosmeceutical actives in the form
of ceramide technology24. It is a mixture of long
chain ceramides, cholesterol, and Sphingokines®
© 2010 PhotoMedex. All Rights Reserved.
Creme de la Copper
signaling molecules. It has been reported that
the mixture of Caprooyl-Phytosphingosine
and Caprooyl-Sphingosine, components of the
Skinmimics mixture, trigger the expression of
genes for late-stage epidermal differentiation to
enhance the synthesis of key sphingolipids in
cultured keratinocytes. Similar results have been
reported in studies with volunteers following
application of the Skinmimics formulation. A
significant reduction in TEWL (Transepidermal
Water Loss) and an increase in skin elasticity has
been measured. These evaluations confirm that
the application of Skinmimics will help mature
skin be revitalized through the combination of
protection, prevention, and regeneration.
Summary
Creme de la Copper combats the effects of
photoaging on the skin. The treatment now
combines Copper Peptide Complex technology
with a new and powerful therapy—advanced
DNA Repair Mitosomes, which contain an enzyme
(OGG1 for 8-oxoguanine DNA glycosylase 1)
produced from the common plant Arabidposis
that recognizes this damaged base (8-oxoguanine) and initiates its removal. This DNA
repair technology is formulated in combination
with Copper Peptide Complex technology to fight
the signs of aging and help to restore the skin’s
youthful texture through repair of the underlying
matrix of the skin.
This new formulation continues to provide the
protection and regeneration properties of the
advanced ceramides of Skinmimics, a mixture
of long chain ceramides, cholesterol, and
Sphingokine signaling molecules. This mixture
of Caprooyl-Phytosphingosine and CaprooylSphingosine are reported to trigger the expression
of genes for late-stage epidermal differentiation
to enhance the synthesis of key sphingolipids in
cultured keratinocytes.
5. Maquart F, X, Simeon A, Pasco S, Monboisse JC.
[Regulation of cell activity by the extracellular matrix: the
concept of matrikines]. Regulation de l’activite cellulaire
par la matrice extracelulaire: le concept de matrikines.
Journal de la Societe de Biologie 1999;193:423-8.
6. Reed MJ, Sage EH. SPARC and the extracellular matrix:
implications for cancer and wound repair. Current topics
in microbiology and immunology 1996;Vol.:81-94.
7. Sage E Helene, Reed M, Funk SE, Truong T, Steadele
M, Puolakkainen P et al. Cleavage of the matricellular
protein SPARC by matrix metalloproteinase 3 produces
polypeptides that influence angiogenesis. The Journal
of biological chemistry 2003;Vol.:-57.
8. Simeon A, Monier F, Emonard H, Wegrowski Y, Bellon G,
Monboisse JC et al. Fibroblase-Cytokine-Extracellular
Matrix Interactions in Wound Repair. Current Topics in
Pathology 1999;93:95-101.
9. Jackson EM. The Importance of Copper in Tissue
Regulation and Repair: A Review. Cosmetic Dermatology
1997;10 (10):35-6.
10. Milne DB. Copper in clinical practice. Clin Lab News
1993;19:80-1.
11. Buffoni F, Pino R, Dal Pozzo A. Effect of tripeptide-copper
complexes on the process of skin wound healing and
on cultured fibroblasts. Archives Internationales de
Pharmacodynamie et de Therapie 1995;Vol.:-60.
12. Huang PJ, Huang YC, Su MF, Yang TY, Huang JR, Jiang
CP. In Vitro Observations on the Influence of Copper
Peptide Aids for the LED Photoirradiation of Fibroblast
Collagen Synthesis. Photomed Laser Surg 2007;25:18390.
13. Maquart FX, Bellon G, Chaqour B, Wegrowski J, Patt
LM, Trachy RE et al. In vivo stimulation of connective
tissue accumulation by the tripeptide-copper complex
glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental
wounds. J Clin Invest 1993;92:2368-76.14. Maquart FX,
Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP.
Stimulation of collagen synthesis in fibroblast cultures
by the tripeptide-copper complex glycyl-L-histidyl-Llysine-copper(2+). FEBS Lett 1988;238:343-6.
15. McCormack MC, Nowak KC, Koch RJ. The effect of
copper tripeptide and tretinoin on growth factor
production in a serum-free fibroblast model. Arch Facial
Plast Surg 2001;3:28-32.
References
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American Academy of Dermatology 60th Annual
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17. Pollard JD, Quan S, Kang T, Koch RJ. Effects of copper
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18. Abdulghani AA, Sherr A, Shirin S, Solodkina G,
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Containing VItamin C, a Copper-Binding Peptide
Cream and Melatonin Compared with Tretinoin on the
Ultrastructure of Normal Skin. Disease Management
and Clinical Outcomes 1998;1(4):136-41.
3. Pickart L, Thaler MM, Millard M. Effect of transition
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chromatography 1979;Vol.:-73.
4. Pickart L, Thaler MM.
Glycylhistidyllysine (GHL)
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A2312-p.668. 1979.
19. Finkey MB, Appa Y, Bhandarkar S. Copper peptide and
skin. Cosmetic Science and Technology Series 27, 549564. 2005. Marcel Dekker, Inc.
© 2010 PhotoMedex. All Rights Reserved.
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Creme de la Copper
20. Leyden JJ, Stevens T, Finkey MB, Barkovic S. Skin Care
Benefits Of Copper Peptide Containing Facial Cream.
American Academy of Dermatology 60th Annual
Meeting February 22-27, 2002 New Orleans, LA . 2002.
21. Leyden JJ, Stevens T, Finkey MB, Barkovic S. Skin Care
Benefits Of Copper Peptide Containing Eye Creams.
American Academy of Dermatology 60th Annual
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22. Barnett Products Corporation Brochure. Roxisomes™,
DNA Protection from Oxygen Radicals. 2009.
23. Wulff BC, Schick JS, Thomas-Ahner JM, Kusewitt DF,
Yarosh DB, Oberyszyn TM. Topical treatment with OGG1
enzyme affects UVB-induced skin carcinogenesis. Photchemistry and photobiology 2008;84:317-21.
24. Skinmimics. 2008. Goldschmidt/degussa Brochure.
Neova and Copper Peptide Complex are registered trademarks of
Procyte Corporation. Skinmimics and Sphingokines are registered
trademarks of Goldschmidt GmbH/degussa.
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